Acute coronary syndromes (ACS) and heart failure (HF) are both associated with complex neurohormonal activation. Commensurate with advances in pharmacological and device therapies for both conditions, the concept of using circulating biomarkers for diagnosis and risk stratification, as well as for targeting and monitoring therapy, has received great attention. Although many novel biomarkers have been identified and evaluated, few have been documented to provide clinically useful incremental information to existing risk markers.1 However, in patients with suspected acute HF, B-type natriuretic peptide (BNP) and N-terminal proBNP have been widely accepted as clinically useful tools. Moreover, among a large number of potential novel prognostic biomarkers in ACS, the BNPs have emerged as the strongest candidates for routine use as a supplement to cardiac-specific troponins.
Acute Heart Failure
The clinical diagnosis of HF can be challenging, particularly in patients presenting with acute shortness of breath in the urgent care setting. Information obtained from clinical history and physical examination, as well as from the electrocardiogram and chest radiograph, may provide valuable clues as to whether HF is the cause of symptoms, but additional diagnostic tests, including echocardiography, may be required to obtain a more definite diagnosis. Currently, the best documented and most widely used clinical application of BNP testing is for the emergency diagnosis of HF in patients presenting with acute dyspnoea. Following the publication of the results of The Breathing Not Properly Multinational study in 2002, BNP measurements have rapidly entered the clinical arena. This multicentre diagnostic test evaluation trial, which included 1,586 patients who visited the emergency department (ED) with a main complaint of acute dyspnoea, used a rapid point-of-care fluorescence immunoassay for BNP determination.2 Diagnosis of HF was adjudicated by cardiologists blinded to the BNP results. BNP levels were found to provide strong and incremental diagnostic information to conventional historical, clinical or other laboratory tests and to have greater diagnostic accuracy for the diagnosis of heart failure than the ED physician using all other available information. Importantly, BNP performed well in patients with an intermediate (20–80%) pre-test probability of HF as evaluated by the ED physician.3 In the subsequent N-terminal Pro-BNP Investigation of Dyspnea in the Emergency Department (PRIDE) study, similar results were published for NT-proBNP. This study included 599 patients presenting to the ED of Massachusetts General Hospital in Boston with acute dyspnoea.4
- Vasan RS, Biomarkers of cardiovascular disease: molecular basis and practical considerations, Circulation, 2006;113(19):2335–62.
- Maisel AS, Krishnaswamy P, Nowak RM, et al., Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure, N Engl J Med, 2002;347(3):161–7.
- McCullough PA, Nowak RM, McCord J, et al., B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study, Circulation, 2002;106(4):416–22.
- Januzzi JL, Jr., Camargo CA, Anwaruddin S, et al., The Nterminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study, Am J Cardiol, 2005;95(8):948–54.
- Januzzi JL, et al., NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study, Eur Heart J, 2006;27(3):330–37.
- Mueller C, Scholer A, Laule-Kilian K, et al., Use of B-Type Natriuretic Peptide in the Evaluation and Management of Acute Dyspnea, N Engl J Med, 2004;350(7):647–54.
- Moe GW, Howlett J, Januzzi JL, Zowall H, N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVECHF study, Circulation, 2007;115(24):3103–10.
- Sabatine MS, Morrow DA, de Lemos JA, et al., Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia, J Am Coll Cardiol, 2004;44(10):1988–95.
- de Lemos JA, Morrow DA, Bentley JH, et al., The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes, N Engl J Med, 2001;345(14):1014–21.
- Omland T, Persson A, Ng L, et al., N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes, Circulation, 2002;106(23):2913–18.
- James SK, Lindahl B, Siegbahn A, et al., N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy, Circulation, 2003;108(3):275–81.
- Heeschen C, et al., N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes, Circulation, 2004;110(20):3206–12.
- Lindahl B, Lindback J, Jernberg T, et al., Serial analyses of Nterminal pro-B-type natriuretic peptide in patients with non-STsegment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy, J Am Coll Cardiol, 2005;45(4):533–41.
- Jernberg T, Lindahl B, Siegbahn A, et al., N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease, J Am Coll Cardiol, 2003;42(11):1909–16.
- James SK, Lindback J, Tilly J, et al., Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV substudy, J Am Coll Cardiol, 2006;48(6):1146-–54.
- Morrow DA, de Lemos JA, Sabatine MS, et al., Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18, J Am Coll Cardiol, 2003;41(8):1264–72.
- Windhausen F, Hirsch A, Sanders GT, et al., N-terminal probrain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy, Am Heart J, 2007;153(4):485–92.